Biology subjects

Robinson, J. E.

Publications and source records attributed to Robinson, J. E..

8 recordsLinked to original sources

bioRxiv2026

Stimulus category is associated with conscious access during motion-induced blindness

Stimuli from different categories, such as faces or letters, differ in semantic content and neural representation. How stimulus category relates to conscious access during perceptual suppression has been studied mainly with binocular rivalry and continuous flash suppression, in which suppression arises from interocular competition. Motion-induced blindness (MIB) is a form of perceptual suppression without interocular competition, in which a static peripheral target intermittently disappears from visual awareness in the presence of a continuously moving background. Here, we tested whether target category affects the temporal dynamics of MIB using human faces, familiar Roman letters, and phase-randomized noise images as targets. Faces disappeared more frequently than noise and showed shorter invisible and visible episodes, whereas overall invisibility fraction and latency to first disappearance did not differ reliably. Letters showed a smaller increase in disappearance rate relative to noise, with no reliable difference in invisible episode duration. These findings reveal systematic category-related differences in the temporal organization of MIB and identify associations between stimulus category and the dynamics of conscious access.

neuroscience↗

bioRxiv2026

Megalin (LRP2), prenatal betamethasone, and injury susceptibility in the developing kidney

Preterm infants undergo postnatal nephrogenesis and are often exposed to gentamicin (gent). Mothers at risk of preterm birth receive betamethasone (beta) to accelerate fetal lung development. Gent cytotoxicity occurs in proximal tubules (PT) after megalin (LRP2)-mediated endocytosis and accumulation. The objective of this study was to evaluate the impact of proximal tubular maturation, impacted by both age and prenatal beta, on injury susceptibility and nephron number in rats. Pups were given toxic gent dosing (100mg/kg) or saline intraperitoneal for 5 days during nephrogenesis (P0-4) or tubular maturation (P6-10). This was repeated with maternal exposure to beta to evaluate impact of beta on injury. Quantitative proteomics analysis revealed significantly higher levels of LRP2 at P10 as compared to P4, correlating with increased injury to gent exposure from P6-10 relative to P0-4. P10 pups exposed to prenatal beta had significantly more LRP2 protein relative to controls, which correlated to more injury after gent exposure at P6-10. Only those exposed to prenatal beta with P6-10 gent demonstrated ~50% nephron reduction. This study supports that tubular maturation is a critical period of vulnerability to gentamicin correlating to LRP2 protein abundance. Prenatal corticosteroids increase the severity of acute and chronic injury in this highest risk exposure group.

developmental biology↗

bioRxiv2025

Genetic activation of ERK2 recapitulates core neurodevelopmental features of Rasopathy syndromes in mice

Germline pathogenic variants that activate the Ras/mitogen-activated protein kinase (MAPK) pathway cause neurodevelopmental disorders called Rasopathies. Because many affected proteins directly regulate Ras, causative mutations may alter other Ras-dependent pathways in addition to MAPK signaling. To better understand which Rasopathy sequelae result from hyperactivation of downstream MAP kinases, we engineered mice with a gain-of-function mutation in the terminal MAP kinase gene Mapk1, which encodes ERK2 and is associated with the recently described genetic syndrome MAPK1-related Rasopathy (MRR). Mapk1 mutant mice successfully modeled key aspects of the human MRR phenotype, including small stature, facial dysmorphism, and impaired cognitive function. Importantly, they recapitulated phenotypes identified in Rasopathy models with upstream Ras activation, such as neurofibromatosis type 1 (NF1): oligodendrocyte lineage defects, reactive astrogliosis, memory deficits, and hypersensitivity to sensory stimuli. These findings emphasize the importance of downstream MAPK signaling in the pathophysiology of neurocognitive symptoms observed in Rasopathy syndromes.

genetics↗

bioRxiv2025

The Latency of a Domain-General Visual Surprise Signal is Attribute Dependent

Predictions concerning upcoming visual input play a key role in resolving percepts. Sometimes input is surprising, under which circumstances the brain must calibrate erroneous predictions so that perception is veridical. Despite the extensive literature investigating the nature of prediction error signalling, it is still unclear how this process interacts with the functionally segregated nature of the visual cortex, particularly within the temporal domain. Here, we recorded electroencephalography (EEG) from humans whilst they viewed static image trajectories containing a bound object that sequentially changed along different visual attribute dimensions (shape and colour). Crucially, the context of this change was designed to appear random (and unsurprising) or violate the established trajectory (and cause a surprise). Event-related potential analysis found no effects of surprise after controlling for cortical adaptation. However, multivariate pattern analyses found whole-brain neural representations of visual surprise that overlapped between attributes, albeit at distinct, attribute-specific latencies. These findings suggest that visual surprise results in whole-brain, generalised (i.e., attribute-agnostic) prediction error responses that conform to an attribute-dependent temporal hierarchy.

neuroscience↗

bioRxiv2025

Microglial brain-derived neurotrophic factor (BDNF) supports the behavioral and synaptogenic effects of ketamine

Microglia have been implicated in the pathogenesis for several psychiatric disorders, yet comparatively little is known about their role in treatments for these conditions. Prior work showed that the rapid-acting antidepressant ketamine increases synaptic density in the prefrontal cortex (PFC), and that brain-derived neurotrophic factor (BDNF) signaling is required for its synaptic and behavioral effects. These studies assumed that neurons were the primary source of BDNF, but other studies have since demonstrated that microglia can produce BDNF in the brain. Still, it remains unclear if microglial BDNF is important for the antidepressant-like effects of ketamine. Our initial studies show that the behavioral and synaptic effects of ketamine are associated with increased Bdnf expression in sorted PFC microglia 24 hours after injection. We then demonstrate that conditional BDNF depletion in microglia (Cx3cr1Cre/+:Bdnffl/fl) reduces GluN2B levels in PFC synaptoneurosomes and attenuates antidepressant-like responses following ketamine treatment compared to genotype controls (Cx3cr1Cre/+:Bdnf+/+). Consistent with this, we found that Cx3cr1Cre/+:Bdnffl/fl mice show no change in dendritic spine density in the PFC following ketamine. These results indicate that microglial BDNF is important for the effects of ketamine on brain and behavior, expanding upon the role of microglia in pharmacological interventions for psychiatric disorders.

neuroscience↗

bioRxiv2022

Ventral striatal dopamine encodes unique properties of visual stimuli in mice

The mesolimbic dopamine system is an evolutionarily conserved set of brain circuits that plays a role in attention, appetitive behavior, and reward processing. In this circuitry, ascending dopaminergic projections from the ventral midbrain innervate targets throughout the limbic forebrain, such as the ventral striatum/nucleus accumbens (NAc). Dopaminergic signaling in the NAc has been widely studied for its role in behavioral reinforcement, reward prediction error encoding, and motivational salience. Less well characterized is the role of dopaminergic neurotransmission in the response to surprising or alerting sensory events. To address this, we used the genetically encoded dopamine sensor dLight1 and fiber photometry to explore the ability of striatal dopamine release in to encode the properties of salient sensory stimuli in mice, such as threatening looming discs. Here, we report that NAc lateral shell (LNAc) dopamine release encodes the rate and magnitude of environmental luminance changes rather than visual stimulus threat level. This encoding is highly sensitive, as LNAc dopamine could be evoked by light intensities that were imperceptible to human experimenters. We also found that light-evoked dopamine responses are wavelength-dependent at low irradiances, independent of the circadian cycle, robust to previous exposure history, and involve multiple phototransduction pathways. Thus, we have further elaborated the mesolimbic dopamine systems ability to encode visual information in mice, which is likely relevant to a wide body of scientists employing light sources or optical methods in behavioral research involving rodents.

neuroscience↗

bioRxiv2019

Machine learning-guided channelrhodopsin engineering enables minimally-invasive optogenetics

We have engineered light-gated channelrhodopsins (ChRs) whose current strength and light sensitivity enable minimally-invasive neuronal circuit interrogation. Current ChR tools applied to the mammalian brain require intracranial surgery for transgene delivery and implantation of invasive fiber-optic cables to produce light-dependent activation of a small volume of brain tissue [~1 mm3]. To enable optogenetics for large brain volumes and without the need for invasive implants, our ChR engineering approach leverages the significant literature of ChR variants to train statistical models for the design of new, high-performance ChRs. With Gaussian Process models trained on a limited experimental set of 102 functionally characterized ChR variants, we designed high-photocurrent ChRs with unprecedented light sensitivity; three of these, ChRger1, ChRger2, and ChRger3, enable optogenetic activation of the nervous system via minimally-invasive systemic transgene delivery with rAAV-PHP.eB, which was not possible previously due to low per-cell transgene copy produced by systemic delivery. These engineered ChRs enable light-induced neuronal excitation without invasive intracranial surgery for virus delivery or fiber optic implantation, i.e. they enable minimally-invasive optogenetics.

bioengineering↗

bioRxiv2018

Prediction-error signals to violated expectations about person identity and head orientation are doubly-dissociated across the dorsal and ventral visual streams

Predictive coding theories of perception suggest the importance of constantly updated internal models of the world in predicting future sensory inputs. One implication of such models is that cortical regions whose function is to resolve particular stimulus attributes should also signal prediction violations with respect to those same stimulus attributes. Previously, through carefully designed experiments, we have demonstrated early-mid latency EEG/MEG prediction-error signals in the dorsal visual stream to violated expectations about stimulus orientation/trajectory, with localisations consistent with cortical areas processing motion and orientation. Here we extend those methods to simultaneously investigate the predictive processes in both dorsal and ventral visual streams. In this MEG study we employed a contextual trajectory paradigm that builds expectations using a series of image presentations. We created expectations about both face orientation and identity, either of which can subsequently be violated. Crucially this paradigm allows us to parametrically test double dissociations between these different types of violations. The study identified double dissociations across the type of violation in the dorsal and ventral visual streams, such that the right fusiform gyrus showed greater evidence of prediction-error signals to Identity violations than to Orientation violations, whereas the left angular gyrus and postcentral gyrus showed the opposite pattern of results. Our results suggest comparable processes for error checking and context updating in high-level expectations instantiated across both perceptual streams. Perceptual prediction-error signalling is initiated in regions associated with the processing of different stimulus properties.\n\nSignificance StatementVisual processing occurs along what and where information streams that run, respectively along the ventral and dorsal surface of the posterior brain. Predictive coding models of perception imply prediction-error detection processes that are instantiated at the level where particular stimulus attributes are parsed. This implies that, for instance, when considering face stimuli, signals arising through violated expectations about the person identity of the stimulus should localise to the ventral stream, whereas signals arising through violated expectations about head orientation should localise to the dorsal stream. We test this in a magnetoencephalography source localisation study. The analysis confirmed that prediction-error signals to identity versus head-orientation occur with similar latency, but activate doubly-dissociated brain regions along ventral and dorsal processing streams.

neuroscience↗